Overweight in liver transplant recipients

This review aims to describe the incidence and prevalence of overweight and obesity after liver transplantation and the consequences associated with it. Literature review consultation was conducted in Medline / PubMed, SciELO, EMBASE and LILACS, with the combination of the following keywords: liver transplantation, overweight, obesity, weight gain. Overweight is incident on more than 60% of patients undergoing liver transplantation and obesity rates exceed 20% in the first year after surgery, during which occurs the largest relative weight gain. Studies have shown that between 60% and 70% of patients undergoing liver transplantation are overweight after the third year, 90% with abdominal obesity. Associated factors are, among others, advanced age, family history of overweight and excess weight prior to liver disease. The contribution of immunosuppressive medication remains controversial. Some of the consequences of overweight are liver steatosis, steatohepatitis, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease and death.


INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION
Liver transplantation is the second most accomplished type of organ transplantation in Brazil, surpassed only by renal transplantation.In 2011, 1,492 liver transplants were performed by 55 teams registered across the nation 1 .It is often the only solution to acute and chronic liver failure, improving the quality of life of patients 2 and increasing life expectancy 3,4 .Over the past two decades, rates of postliver transplantation survival increased to 85% in five years 3 and to 56% after 20 years 4 , mainly due to advances in surgical techniques, in immune management and in pre, peri and postoperative care 5 .
However, the increased survival of patients undergoing liver transplantation was accompanied by the increasing prevalence of chronic diseases, usually higher than the prevalence found in the general population 6 .In this context, we highlight the excessive weight gain experienced by these patients, causing overweight and obesity.There are reports on obesity in 40% of the population already in the first post-transplant year 7 , and after three years of operation about 70% of patients have excess body weight 8 .Although no study has been able to demonstrate the relationship between overeating and posttransplant weight gain [9][10][11][12] , it is known that patients undergoing liver transplantation rediscover the appetite and pleasure of old eating habits after months of restrictions 13 .Also, they feel better and are able to feed in appreciable quantities.At the same time, they feel eager to regain the weight lost during the months of waiting for transplantation 14,15 , since 75% of them are malnourished during this period 16 .Moreover, many patients do not return to work after surgery 17 and those surviving for long periods have levels of daily physical activity significantly lower than the general population 4.Besides these factors, all patients submitted to transplantation use immunosuppressive drugs, among which mainly cyclosporine or tacrolimus and, at least initially, corticosteroids.All these drugs are implicated in the genesis of posttransplant excessive weight gain and obesity 18,19 .Although this gain can not affect the statistics of survival of patients in the short term, it is certainly involved in the incidence of diabetes mellitus, dyslipidemia, hypertension and metabolic syndrome in this population 20 .This morbidity exposes patients to increased risk of heart and kidney diseases, as well as nonalcoholic graft steatohepatitis.All have important consequences on longterm mortality 21 .
Thus, this revision work was elaborated in order to describe the weight gain, incidence and prevalence of overweight and obesity after liver transplantation, as well as the risk factors described for this morbidity and its consequences.Weight gain after liver transplantation is crucial for the recovery of the patients' nutritional status.However, they usually gain more weight than they should.In a study of 597 patients 8, the average weight gain increased from 1.8 kg 9.5 kg six months to three years after transplantation, leading to a prevalence of about 70% overweight (BMI> 25 kg/m 2 ).
The incidence of obesity in the first postoperative year ranges from 15.5% to 40.7% 7,8 , depending on the definition used, and continues to grow over the years after transplantation 7,8 .Some authors have reported rates of overweight of 60% on the second year 11 and 70% on the third 8 .The works that have studied the incidence and prevalence of overweight and obesity after liver transplantation were summarizer in Table 1.
The first postoperative year seems to be responsible for most of the weight gained after the operation 8,10,22   .Patients seem to recover most of the weight lost during liver disease already in the first post-transplant year; 45% of them are overweight at the end of the first year versus 21% at the first post-transplant outpatient visit, and 43% prior to liver disease 23 .
Patients with longer transplant time have an even higher prevalence of overweight 24 .In a study with 143 patients undergoing liver transplantation with a median of four years since surgery, 58.1% were classified as having overweight by BMI and 69.9% by body composition.In the same study, 21% of individuals were classified as obese by BMI (e" 30 kg/m2) and 37.8% by body composition 25 .
Although the prevalence of overweight and obesity are in clear ascendancy in recent years worldwide and in Brazil, yet the prevalence in the population undergoing transplantation is higher than in the general one.According to the latest data from the 2008 2009 Household Budget Survey, 50% of the adult Brazilian population has overweight, and 14.7%, obesity 26 .
Still considering excess body weight, few studies have evaluated the prevalence of abdominal obesity in patients undergoing transplantation.In the study by Bianchi et al. 27 , with 296 patients, the prevalence of waist circumference greater than 88cm for women and 102cm for men was 32 % 28 .In the study by Anastácio et al. 25 , 41.5% of the individuals were thus classified, and 88% had some degree of abdominal obesity (waist circumference greater than 80cm for women and 90cm for men) 25 .

FACTORS ASSOCIATED TO FACTORS ASSOCIATED TO FACTORS ASSOCIATED TO FACTORS ASSOCIATED TO FACTORS ASSOCIATED TO WEIGHT GAIN, OVERWEIGHT WEIGHT GAIN, OVERWEIGHT WEIGHT GAIN, OVERWEIGHT WEIGHT GAIN, OVERWEIGHT WEIGHT GAIN, OVERWEIGHT AND OBESITY AND OBESITY AND OBESITY AND OBESITY AND OBESITY
The factors described are often older age 8,29 , family history of overweight, high BMI prior to the disease 8,22,30 , post-transplant hypometabolism 8,10 , post-transplant physical inactivity 10 , high donor BMI 22 , being married 22,25 , few hours slept 25 and less dietary calcium intake 25 .
Some authors demonstrated greater weight gain in patients undergoing liver transplantation for chronic liver diseases compared with those who were transplanted due to fulminant hepatic failure 8 .This is consistent with the theory of regain of the weight lost while waiting for transplantation.The highest incidence of obesity has also been observed in patients with a history of overweight or higher BMI prior to liver transplantation 8,22,24,25,31 .
The use of immunosuppressive drugs as a risk factor for excess weight after liver transplantation is still controversial.Some studies have found an association with cyclosporine 27,32 and steroids 22 and weight gain or being overweight, but not all 7,8,24 .
The contribution of the lower energy expenditure for the formation of overweight and obesity in patients undergoing transplantation also remains unclear.Richardson et al. 12 followed 23 patients after liver transplantation.They found a significant reduction in resting energy expenditure nine months after liver transplantation when compared with the pre-transplant period and controls.These authors also observed that the reduced resting energy expenditure after transplantation was an important predictor of increasing body fat mass after liver transplantation, though this association has not always been observed 33 .Although it is not yet known whether it does or does not decrease after transplantation, certainly, the total energy expenditure of these individuals is reduced postoperatively.Patients undergoing liver transplantation generally reduce the level of physical activity.Besides, they retire when seriously ill while on the waiting list for transplantation.After the operation, most do not return to work 17 and a minority have reasonable levels of physical activity, 24% according to Painter et al. 34 .Other authors also found that levels of physical activity in patients undergoing liver transplantation are significantly lower than those of the general population 4 .
There are few data on food intake in liver transplant recipients.Nevertheless, none of the studies showed an association of dietary caloric intake with weight changes 8,10,11,25 .This is possibly due to the methods used, since intake is usually assessed at the time of data collection and not continuously.Studies on the role of steroids in weight gain suggest that they stimulate appetite and increase intake of high-fat candies and food 35 .Thus, patients tend to consume excess calories.In addition, patients undergoing liver transplantation feel freed from pre-transplant restrictions dietary and no longer have anorexia.They also have a higher sense of well-being and anxiety to regain the weight lost while waiting for transplantation 15 .Still, it is likely that patients return to old eating habits; the contribution of a history of overweight has been widely described as a risk factor for excessive weight gain and obesity 8,22,24,25,31 .

Incidence and prevalence of excess weight, overweight and obesity after liver transplantation.
There are several implications of obesity in patients undergoing liver transplantation.Studies have shown that the obesity of donor and recipient may influence operative results [36][37][38][39][40][41][42] .Pre-obese patients are more likely, to develop primary graft dysfunction, delayed graft function after the operation and have increased risk of death 36,37 .These findings have not been universal, however, 38 .
Obesity can also affect the graft in the late postoperative period.In patients with general indications for liver transplantation, the incidence of steatosis ranges from 18% 43 to 40% 44 and the incidence of non-alcoholic steatohepatitis, from 9% 43 to 13% 44 .Excess weight has been considered a risk factor for such types of involvement.Seo et al. 43 observed that 83% of patients who developed nonalcoholic fatty liver disease had weight gain 10% higher compared with pre-transplant BMI.Lim et al. 44 also observed that liver transplant recipients who developed nonalcoholic steatohepatitis had significantly higher BMI (32.5 ± 4.3 kg/ m 2 ) than those who did not develop this condition (22.9 ± 0.7 kg/m 2 ).
In addition, excessive weight gain and excess weight are certainly related to comorbidities, such as dia-betes, dyslipidemia, hypertension, metabolic syndrome, osteoarthritis and sleep apnea.They expose patients to increased risk of cardiovascular and renal diseases, and graft steatohepatitis 20 , as it happens in the general population.Moreover, higher rates of such conditions are found in patients moderately (BMI between 35-40kg/m 2 ) and severely obese (BMI > 40kg/m 2 ) after five years of operation 45 .

FINAL CONSIDERATIONS FINAL CONSIDERATIONS FINAL CONSIDERATIONS FINAL CONSIDERATIONS FINAL CONSIDERATIONS
Patients undergoing liver transplantation experience excessive weight gain, especially in the first post-transplant year, increasing over the years.Factors described as associated with weight gain and excess posttransplant weight are multiple, but the contribution of immunosuppressive medication remains controversial.Overweight and obesity after liver transplantation are associated with different consequences, ranging from higher recipient mortality to the development of various conditions -fatty liver, steatohepatitis, diabetes, hypertension, dyslipidemia and cardiovascular disease.Programs to prevent excessive weight gain should be implemented by multidisciplinary teams in the centers where these patients are followed.